Abstract

A patent foramen ovale (PFO), present in ~40% of the general population, is a potential source of right-to-left shunt that can impair pulmonary gas exchange efficiency [i.e., increase the alveolar-to-arterial PO2 difference (A-aDO2)]. Prior studies investigating human acclimatization to high-altitude with A-aDO2 as a key parameter have not investigated differences between subjects with (PFO+), or without a PFO (PFO−). We hypothesized that in PFO+ subjects A-aDO2 would not improve (i.e., decrease) after acclimatization to high-altitude compared to PFO− subjects. Twenty-one (11 PFO+) healthy sea-level residents were studied at rest and during cycle ergometer exercise at the highest iso-workload achieved at sea-level (SL), after acute transport to 5260 m (ALT1), and again at 5260 m after 16-days of high-altitude acclimatization (ALT16). In contrast to PFO− subjects, PFO+ subjects had: 1) no improvement in A-aDO2 at rest and during exercise at ALT16 compared to ALT1, 2) no significant increase in resting alveolar ventilation, or alveolar PO2, at ALT16 compared to ALT1, and consequently had 3) an increased arterial PCO2 and decreased arterial PO2 and arterial O2 saturation at rest at ALT16. Furthermore, PFO+ subjects had an increased incidence of acute mountain sickness (AMS) at ALT1 concomitant with significantly lower peripheral O2 saturation (SpO2). These data suggest that PFO+ subjects have increased susceptibility to AMS when not taking prophylactic treatments, that right-to-left shunt through a PFO impairs pulmonary gas exchange efficiency even after acclimatization to high-altitude, and that PFO+ subjects have blunted ventilatory acclimatization after 16 days at altitude compared to PFO− subjects.